PLEKHG6

pleckstrin homology and RhoGEF domain containing G6, the group of Dbl family Rho GEFs|Pleckstrin homology domain containing

Basic information

Region (hg38): 12:6310435-6328506

Links

ENSG00000008323 ∙ NCBI:55200 ∙ OMIM:611743 ∙ HGNC:25562 ∙ Uniprot:Q3KR16 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLEKHG6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLEKHG6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			69	4		73
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding				1	1	2
Total	0	0	70	5	1

Variants in PLEKHG6

This is a list of pathogenic ClinVar variants found in the PLEKHG6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-6312233-G-A		not specified	Uncertain significance (Sep 01, 2021)
12-6312239-G-A		not specified	Uncertain significance (Jun 21, 2023)
12-6312293-T-C		not specified	Uncertain significance (Dec 14, 2023)
12-6312302-C-T		not specified	Uncertain significance (Dec 08, 2023)
12-6312303-G-A		not specified	Uncertain significance (Aug 28, 2023)
12-6313162-C-T			Likely benign (Apr 01, 2022)
12-6313168-TG-T		PLEKHG6-related disorder	Benign (Apr 06, 2022)
12-6313636-G-A		not specified	Uncertain significance (Jun 28, 2022)
12-6313638-C-A		not specified	Uncertain significance (Feb 15, 2023)
12-6313639-G-A		not specified	Uncertain significance (Feb 15, 2023)
12-6313645-G-A		not specified	Uncertain significance (Jan 12, 2024)
12-6313652-G-T		not specified	Uncertain significance (Aug 01, 2022)
12-6313690-G-A		not specified	Uncertain significance (Jul 09, 2021)
12-6313728-G-A		not specified	Uncertain significance (Jun 16, 2023)
12-6313740-G-A		not specified	Uncertain significance (Aug 02, 2022)
12-6313774-C-G		not specified	Uncertain significance (Jan 23, 2023)
12-6313776-A-G		not specified	Uncertain significance (Jun 24, 2022)
12-6315037-G-T		not specified	Uncertain significance (Apr 12, 2022)
12-6315043-C-A		not specified	Uncertain significance (Sep 12, 2023)
12-6315062-A-G		not specified	Uncertain significance (Mar 20, 2023)
12-6315069-G-A		not specified	Uncertain significance (Jan 23, 2023)
12-6315089-C-T		not specified	Uncertain significance (Dec 13, 2022)
12-6315116-G-A		not specified	Uncertain significance (Jun 07, 2023)
12-6315566-G-A		not specified	Uncertain significance (May 23, 2023)
12-6315632-C-T		not specified	Uncertain significance (Jan 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLEKHG6	protein_coding	protein_coding	ENST00000396988	15	18071

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.72e-19	0.227	125656	1	91	125748	0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.000607	462	462	1.00	0.0000291	4975
Missense in Polyphen		71	94.277	0.7531		1053
Synonymous	-0.680	200	188	1.06	0.0000109	1691
Loss of Function	1.55	35	46.4	0.755	0.00000330	410

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000337	0.000336
Ashkenazi Jewish	0.00	0.00
East Asian	0.000394	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000315	0.000308
Middle Eastern	0.000394	0.000326
South Asian	0.00143	0.00127
Other	0.000339	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor activating the small GTPase RHOA, which, in turn, induces myosin filament formation. Also activates RHOG. Does not activate RAC1, or to a much lower extent than RHOA and RHOG. Part of a functional unit, involving PLEKHG6, MYH10 and RHOA, at the cleavage furrow to advance furrow ingression during cytokinesis. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with EZR, required for normal macropinocytosis. {ECO:0000269|PubMed:16721066, ECO:0000269|PubMed:17881735}.
• Pathway: Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.0857

Intolerance Scores

• loftool: 0.984
• rvis_EVS: -0.79
• rvis_percentile_EVS: 12.63

Haploinsufficiency Scores

• pHI: 0.0691
• hipred: N
• hipred_score: 0.372
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.296

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Plekhg6

Gene ontology

• Biological process: regulation of Rho protein signal transduction;positive regulation of GTPase activity
• Cellular component: spindle pole;cytoplasm;centrosome;microvillus;cell junction;cleavage furrow
• Molecular function: Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding